177Lu-PSMA-617 and 177Lu-PSMA I&T (collectively termed 177Lu-PSMA) are currently being used for the treatment of selected metastatic castration-resistant prostate cancer (mCRPC) patients with PSMA PET-positive disease, but biomarkers for these agents remain incompletely understood. Methods: Pretreatment circulating tumor DNA (ctDNA) samples were collected from 44 mCRPC patients receiving 177Lu-PSMA treatment. Prostate-specific antigen responders and nonresponders were assessed relative to the ctDNA findings at baseline. Results: The ctDNA findings indicated that nonresponders were more likely to have gene amplifications than were responders (75% vs. 39.2%, P = 0.03). In particular, amplifications in FGFR1 (25% vs. 0%, P = 0.01) and CCNE1 (31.2% vs. 0%, P = 0.001) were more likely to be present in nonresponders. CDK12 mutations were more likely to be present in nonresponders (25% vs. 3.6%, P = 0.05). Conclusion: Our analyses indicate that ctDNA assays may contain specific biomarkers predictive of response or resistance for 177Lu-PSMA-treated mCRPC patients. Additional confirmatory studies are required before clinicians can use these findings to make personalized treatment decisions.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2023 Sep 28 [Epub ahead of print]
Oliver Sartor, Elisa Ledet, Minqui Huang, Jennifer Schwartz, Alex Lieberman, Brian Lewis, Jodi Layton, Pedro Barata, Albert Jang, Madeline Hawkins, Olivia Pocha, Sree Lanka, Kendra Harris
Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana; ., Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana.